Cellular immune responses during high-dose interferon-alpha induction therapy for hepatitis C virus infection

J Infect Dis. 2009 Mar 15;199(6):819-28. doi: 10.1086/597072.

Abstract

Background: The effect that high-dose interferon (IFN)-alpha induction therapy for hepatitis C virus (HCV) infection has on cellular immune responses is currently unknown.

Methods: Thirty-one treatment-naive patients with chronic HCV infection received amantadine and ribavirin, combined with 6 weeks of high-dose IFN-alpha-2b induction therapy followed by weekly pegylated IFN-alpha-2b, for 24 or 48 weeks. Using IFN-gamma and interleukin (IL)-2 enzyme-linked immunospot (ELISpot) assays, we analyzed the pattern of cytokine secretion by structural and nonstructural HCV- and cytomegalovirus (CMV)-specific T cells before, during, and after therapy.

Results: HCV-specific T cell responses, which were predominantly IFN-gamma secreting and which correlated with alanine transaminase levels (r2 = 0.45; P = .001), were found before treatment in 10 of 15 patients with a sustained virological response (SVR) and in 11 of 16 in the non-SVR group. There was a striking loss of IFN-gamma and IL-2 HCV-specific T cells during therapy, predominantly in the SVR group. This response recovered after cessation of therapy, regardless of outcome. Suppression of CMV-specific T cell responses, in addition to total lymphocyte counts, was also observed.

Conclusions: High-dose IFN-alpha induction therapy leads to a profound decline in IL-2- and IFN-gamma-secreting HCV- and CMV-specific T cells. These data indicate that restoration of T cell responses is unlikely to be causally linked to an early response or SVR to therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / immunology
  • Antiviral Agents / therapeutic use
  • Female
  • Hepacivirus / isolation & purification
  • Hepacivirus / physiology*
  • Hepatitis C / drug therapy*
  • Hepatitis C / immunology*
  • Humans
  • Immunity, Cellular*
  • Interferon-alpha / immunology
  • Interferon-alpha / therapeutic use*
  • Kinetics
  • Male
  • Middle Aged
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Virus Replication / drug effects
  • Young Adult

Substances

  • Antiviral Agents
  • Interferon-alpha